"Introduction Aspirin-intolerant urticaria (AIU) presents with the immediate onset of urticaria after aspirin ingestion persisting for 1 to more than 6 weeks depending upon the severity. Adenosine is a potent and ubiquitous signaling nucleoside that is generated in response to cellular stress and damage and is therefore increased during episodes of tissue hypoxia and inflammation.

Material and Methods To investigate the biological role of adenosine A3 receptor (ADORA3) in the pathogenesis of AIU, we performed an SNP haplotype-based case-control association study in 373 AIU patients including 180 aspirin-intolerant chronic urticaria (AICU), 193 aspirin-intolerant acute urticaria (AIAU), and 178 normal controls (NC) based on the Korean population. The functional effects of genetic polymorphisms in ADORA3 were analyzed by luciferase reporter assay, electrophoretic mobility shift assay (EMSA), and real-time PCR for the mRNA expression in PBMC of AIU patients.

Results The haplotype [T-1050C-564] frequency of ADORA3 gene showed significantly higher in AIAU group than in AICU and NC groups (p = 0.047, for AIAU vs. AICU; p = 0.005, for AIAU vs. NC). The transcriptional activity of -564 C allele was higher than T allele, and EMSA finding showed that NF-κB bound more tightly to the C allele sequence than to the T allele sequence by EMSA. Moreover, in PBMC obtained from AIU patients, mRNA expression of ADORA3 in patients with haplotype [T-1050C-564] showed significantly higher than those without it in dominant model (p = 0.033).

Conclusion These results indicate that the haplotype [T-1050C-564] of ADORA3 could affect the clinical presentation of AIAU.